Phosphatidylinositol 3-Kinase C2α Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis

摘要

Neurotransmitter release and hormonal secretion are highly regulated processes culminating in the calcium-dependent fusion of secretory vesicles with the plasma membrane. Here, we have identified a role for phosphatidylinositol 3-kinase C2α (PI3K-C2α) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2α is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2α function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2α enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2α mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2α is required for acquisition of fusion competence in neurosecretion.